Grantee Research Project Results
2006 Progress Report: Evaluating Nanoparticle Interactions with Skin
EPA Grant Number: R831715Title: Evaluating Nanoparticle Interactions with Skin
Investigators: Monteiro-Riviere, Nancy A. , Riviere, Jim E.
Institution: North Carolina State University
EPA Project Officer: Hahn, Intaek
Project Period: September 18, 2004 through September 30, 2007
Project Period Covered by this Report: September 18, 2005 through September 30, 2006
Project Amount: $328,972
RFA: Exploratory Research to Anticipate Future Environmental Issues: Impacts of Manufactured Nanomaterials on Human Health and the Environment (2003) RFA Text | Recipients Lists
Research Category: Safer Chemicals , Nanotechnology , Human Health
Objective:
The focus of this research is to assess the nature of interaction between manufactured nanoparticles and the skin, including dermal absorption and cutaneous toxicity, as well as the ability to distribute to the skin after systemic exposure. All studies will be conducted in three well-characterized in vitro skin models: human skin keratinocyte cell cultures, porcine skin flow-through diffusion cells, and the isolated perfused porcine skin flap (IPPSF).
Progress Summary:
A primary route of potential occupational and environmental exposure to manufactured nanomaterials is the skin. Absorption across skin could result in systemic exposure while penetration into skin could cause local dermatological effects. Multi-walled carbon nanotubes (MWCNT), fullerene substituted phenylalanine derivative (Baa-(FITC)-NLS), and quantum dots (QD) of different sizes and surface chemistries were studied with respect to their interactions with skin, focusing both on their ability to cross the protective stratum corneum barrier as well as interact with the skin’s viable cell population, keratinocytes. The biological effects of these nanomaterials were studied using transmission electron microscopy, laser confocal microscopy, proteomics, as well as standard cellular viability and cytokine assays. The interactions of nanomaterials in cultured human keratinocytes, absorption of nanomaterials through skin and confocal images depicting localization within skin have been shown. MWCNT were primarily localized in intracytoplasmic vacuoles, and induced the release of the proinflammatory cytokine interleukin 8 (IL-8) from keratinocytes in a time-dependent manner. Proteomic analysis suggests perturbations of proteins associated with vesicular trafficking and exocytosis, a finding consistent with the transmission electron microscopic changes. Substituted fullerenes were detected penetrating through intact skin and caused an inflammatory response based on cytokine levels of expression. In developing new applications involving nanomaterials and nanoparticles, it is important to adequately assess all factors that can lead to increased nanoparticle exposure. Additional studies with these fullerenes were continued via activities that involve repetitive motion that can intensify mechanical loads that are applied to the skin. Constant repetitive hand movements may alter the permeability barrier of skin and thus increase risks associated with exposure to nanoparticles. In order to investigate the relationship between mechanical stressors and nanoparticle exposure, a flexing apparatus was designed to simulate repetitive wrist motion. Finally, it was demonstrated that commercially available QD with diverse surface coatings also penetrated the skin and caused cytotoxic and inflammatory effects, which correlated to their size and surface properties. The disposition of QD in tissues is important for developing nanotechnology-based drug delivery systems as well as defining their toxicological profile. The IPPSF was used to determine whether intra-arterially infused QD with different surface coatings could affect uptake and cutaneous distribution. All of these studies confirm that a variety of manufactured nanoparticles, not optimized for en hanced biological effects, are capable of penetrating skin cells and intact skin. This research has identified the potential toxicity of some nanoparticles that could have profound implications for researchers, manufacturers, medical personnel, and the general population alike.
Future Activities:
We will continue to conduct research with quantum dots having different surface coatings in the IPPSF. The disposition and pharmacokinetics of nanoparticles in tissues are crucial parameters for targeting nanotechnology-based drug delivery systems as well as defining their toxicological profile. In addition, quantum dots are an excellent model nanomaterial because they can be synthesized with varying surface coatings that modulate disposition, as well as being amenable to quantification in tissues due to their fluorescent intensity. Therefore, a physiological-based pharmacokinetic model of QD uptake and release from skin, using continuously monitored arterial and venous QD concentrations, will be developed.
Journal Articles on this Report : 16 Displayed | Download in RIS Format
Other project views: | All 119 publications | 22 publications in selected types | All 17 journal articles |
---|
Type | Citation | ||
---|---|---|---|
|
Leduc PR, Wong MS, Ferreira PM, Groff RE, Haslinger K, Koonce MP, Lee WY, Love JC, McCammon JA, Monteiro-Riviere NA, Rotello VM, Rubloff GW, Westervelt R, Yoda M. Towards an in vivo biologically inspired nanofactory. Nature Nanotechnology 2007;2(1):3-7. |
R831715 (2006) R831712 (Final) |
Exit Exit |
|
Monteiro-Riviere NA, Inman AO, Wang YY, Nemanich RJ. Surfactant effects on carbon nanotube interactions with human keratinocytes. Nanomedicine: Nanotechnology, Biology, and Medicine 2005;1(4):293-299. |
R831715 (2005) R831715 (2006) R831710 (Final) |
Exit |
|
Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY, Riviere JE. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicology Letters 2005;155(3):377-384. (Most highly cited paper by Elsevier publishers.). |
R831715 (2005) R831715 (2006) |
Exit Exit Exit |
|
Monteiro-Riviere NA, Inman AO. Challenges for assessing carbon nanomaterial toxicity to the skin. Carbon 2006;44(6):1070-1078. |
R831715 (2005) R831715 (2006) R831712 (Final) |
Exit |
|
Oberdorster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Particle and Fibr Toxicology 2005;2(8):1-35. |
R831715 (2005) R831715 (2006) |
not available |
|
Rouse JG, Yang J, Barron AR, Monteiro-Riviere NA. Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes. Toxicology In Vitro 2006;20(8):1313-1320. |
R831715 (2006) R831712 (Final) |
Exit Exit |
|
Rouse JG, Yang J, Ryman-Rasmussen JP, Barron AR, Monteiro-Riviere NA. Effects of mechanical flexion on the penetration of fullerene amino acid-derivatized peptide nanoparticles through skin. Nano Letters 2007;7(1):155-160. |
R831715 (2006) R831712 (Final) |
Exit |
|
Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicological Sciences 2006;91(1):159-165. |
R831715 (2006) R831712 (Final) |
Exit Exit Exit |
|
Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes. Journal of Investigative Dermatology 2007;127(1):143-153. |
R831715 (2006) R831712 (Final) |
Exit Exit Exit |
|
Walker GM, Monteiro-Riviere NA, Rouse J, O'Neil AT. A linear dilution microfluidic device for cytotoxicity assays. Lab on a Chip 2007;7(2):226-232. |
R831715 (2006) R831712 (Final) |
Exit |
|
Wei C, Lyubchenko YL, Ghandehari H, Hanes J, Stebe KJ, Mao H-Q, Haynie DT, Tomalia DA, Foldvari M, Monteiro-Riviere N, Simeonova P, Nie S, Mori H, Gilbert SP, Needham D. New technology and clinical applications of nanomedicine: highlights of the second annual meeting of the American Academy of Nanomedicine (Part I). Nanomedicine: Nanotechnology, Biology and Medicine 2006;2(4):253-263. |
R831715 (2006) |
|
|
Wei W, Sethuraman A, Jin C, Monteiro-Riviere NA, Narayan RJ. Biological properties of carbon nanotubes. Journal of Nanoscience and Nanotechnology 2007;7(4-5):1284-1297. |
R831715 (2006) R831712 (Final) |
Exit |
|
Witzmann FA, Monteiro-Riviere NA. Multi-walled carbon nanotube exposure alters protein expression in human keratinocytes. Nanomedicine: Nanotechnology, Biology, and Medicine 2006;2(3):158-168. |
R831715 (2006) R831712 (Final) |
Exit |
|
Xia X-R, Monteiro-Riviere NA, Riviere JE. Trace analysis of fullerenes in biological samples by simplified liquid-liquid extraction and high-performance liquid chromatography. Journal of Chromatography A 2006;1129(2):216-222. |
R831715 (2006) R831712 (Final) |
Exit Exit |
|
Zhang LW, Zeng L, Barron AR, Monteiro-Riviere NA. Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes. International Journal of Toxicology 2007;26(2):103-113. |
R831715 (2006) R831712 (Final) |
Exit |
|
Zhang LW, Yu WW, Colvin VL, Monteiro-Riviere NA. Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. Toxicology and Applied Pharmacology 2008;228(2):200-211. |
R831715 (2006) |
Exit Exit |
Supplemental Keywords:
nanotoxicity, nanotoxicology, quantum dots, nanomaterials, skin, skin penetration, human epidermal keratinocytes, nanomaterial inflammation.,, Scientific Discipline, Health, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biology, Risk Assessment, toxicology, carbon fullerene, cutaneous toxicity, nanotechnology, iron oxide nanocrystals, dermal contact, human exposure, cellular response to nanoparticles, exposure assessment, human health risk, oxidative stressRelevant Websites:
http://www.eurekalert.org/nanotalk ExitProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.